A Retrospective Analysis of Eosinophilia as a Predictive Marker of Response and Toxicity to Cancer Immunotherapy

Krishnan, Tharani; Tomita, Yoko; Roberts‐Thomson, Rachel

doi:10.2144/fsoa-2020-0070

Cited by 26 publications

(24 citation statements)

References 17 publications

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“…The eosinophil count was 0.12 ± 0.22 *10 9 /L in patients with rash − and 0.17 ± 0.17 *10 9 /L in patients with rash + ( P = .463). Eosinophilia was defined as a peripheral blood absolute eosinophil count greater than 0.5*10 9 /L 13 . Accordingly, a total of five (5.0%) patients were identified as having eosinophilia (>0.5*10 9 /L), among which only one patient had rash ( P = .379) (Supporting Table Table 1).…”

Section: Resultsmentioning

confidence: 99%

Immune‐related adverse events predict responses to PD‐1 blockade immunotherapy in hepatocellular carcinoma

Xing

Wei

et al. 2021

Intl Journal of Cancer

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Immune checkpoint blockade has demonstrated remarkable efficacy in hepatocellular carcinoma (HCC) but is also commonly accompanied by immune‐related adverse events (irAEs). However, the association between irAEs and antitumor efficacy in HCC patients remains unknown. All patients with HCC treated with anti‐PD‐1 antibodies from July 2018 to November 2019 were analyzed and divided into different groups according to their irAEs' status. In total, 101 HCC patients, including 21 (20.8%) patients who presented with irAEs (irAEs+), were enrolled. Among the adverse events, rash (n = 9, 8.9%) was the most frequent irAE, followed by mucositis (n = 3, 3.0%) and thyroiditis (n = 3, 3.0%). Patients in the irAEs+ group showed a higher tumor response rate than those in the irAEs− group (overall response rate: 28.6% vs 6.3%, P = .011; disease control rate: 85.7% vs 60.0%, P = .028). The median progression‐free survival (PFS) times were 14.8 months in the irAEs+ group and 4.1 months in the irAEs− group (P < .001). Further analysis based on the presence or absence of rash showed that the PFS of the patients in the irAEs+/rash+ group was better than that of those in the irAEs+/rash− or irAEs− group (all P < .05). Multivariate analysis showed that irAEs were an independent prognostic factor for PFS (hazard ratio [HR]: 0.22, P = .002). Thus, the occurrence of irAEs, especially rash, was associated with markedly improved PFS. Awareness of irAEs may help classify the subtype of HCC patients with an unprecedented survival benefit from anti‐PD‐1 antibodies.

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Section: Resultsmentioning

confidence: 99%

Immune‐related adverse events predict responses to PD‐1 blockade immunotherapy in hepatocellular carcinoma

Xing

Wei

et al. 2021

Intl Journal of Cancer

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“…The fact that we did not find a correlation with response may be due to the retrospective nature of the study with incomplete data collection during patients' follow-up. On the other hand, a correlation between eosinophilia (i.e., AEC > 0.5 cells/mL) and immune-related toxicity (p = 0.0042) has been demonstrated in a retrospective series including 146 patients with various solid tumor types treated with anti-PD(L)-1 [37]. As a correlation between eosinophils and response to ICI and between eosinophils and toxicity under ICI were shown, it is tempting to think that both clinical results (response and toxicity) are two sides of one phenomenon: immune (re-)activation.…”

Section: Discussionmentioning

confidence: 99%

White Blood Cells in Patients Treated with Programmed Cell Death-1 Inhibitors for Non-small Cell Lung Cancer

Sibille

Henket

Corhay

et al. 2021

Lung

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Purpose To investigate whether eosinophils and other white blood cell subtypes could be used as response and prognostic markers to anti-Programmed cell Death-1 or anti-PD-Ligand-1 treatments in non-small cell lung cancer patients. Methods We retrospectively analyzed data from the NSCLC patients consecutively treated at our hospital with a PD-1/PD-L1 inhibitor in monotherapy for advanced disease. A total of 191 patients were evaluated at three time-points to investigate any relation between tumor response and WBC counts. Results Baseline WBC and subtypes did not differ according to the type of response seen under treatment. A higher relative eosinophil count (REC) correlated with more objective responses (p = 0.019 at t1 and p = 0.014 at t2; OR for progression = 0.54 and 0.53, respectively) independently of the smoking status, PD-L1 status, and immune-related toxicity (IRT). Higher REC was also associated with a longer duration of treatment (p = 0.0096). Baseline absolute neutrophil count was prognostic (p = 0.049). At t1 relative lymphocytes, absolute and relative neutrophils, and neutrophil-to-lymphocyte ratio were prognostic (p = 0.044, p = 0.014, p = 0.0033, and p = 0.029, respectively). Conclusion Our results show that in NSCLC patients anti-PD-1/PD-L1 therapy induces an early increase only in blood eosinophils, more prominent in responding patients and independent of the smoking status, PD-L1 status, and IRT. Eosinophils are also associated with a longer duration of treatment. Furthermore, our data support a prognostic role of neutrophils, lymphocytes, and their ratio for NSCLC patients with advanced disease treated with PD(L)-1 blockade.

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“…This is because eosinophils may have antitumoral effects in the tumor microenvironment by promoting NK cell and T cell recruitment and direct cytotoxicity by production of granzymes and other cytotoxic proteins [47]. A similar report highlighted that patients experiencing treatment toxicity were more likely to have eosinophilia during the course of treatment [17]. Interestingly, Jodai et al reported that the interaction between PD-1 receptors with both programmed cell death receptor ligand 1 (PD-L1) and PD-L2 on lung dendritic cells might explain the mechanism of eosinophilic pneumonia: the binding of PD-1 to PD-L2 on the dendritic cells may activate pulmonary inflammation induced by Th2 cells which produces interleukin (IL) 4, 5, and 13, eventually resulting in eosinophilic activation [48].…”

Section: Discussionmentioning

confidence: 95%

“…Among the many factors under study, our interest has centered in on the role of eosinophils. As already mentioned above, the role of this white blood cell subpopulation as a potential cellular biomarker in cancer therapy has been highlighted in several studies [15][16][17][36][37][38][39][40][41][42][43].…”

Section: Introductionmentioning

confidence: 94%

“…Nakamura et al proved that baseline AEC > 240/µL was the most useful indicator to assess endocrine irAEs in patients with metastatic melanoma (mM) treated with ICIs, and that a higher relative eosinophil count (REC) after 1 month of therapy was significantly correlated with the occurrence of endocrine irAEs [16]. In the study by Krishnan et al, patients who experienced eosinophilia during treatment with ICIs were more likely to gain disease control and develop toxicity [17]. Other predictive biomarkers of toxicity investigated include subpopulations of lymphocytes [18][19][20], various cytokines, such as interleukin (IL) 6 and 17 [19,21,22], C-reactive protein (CRP) [23,24], multiple chemokines [25], autoantibodies [26][27][28][29][30][31], single-nucleotide polymorphisms (SNPs) [32,33], microRNA [34], the microbiome [19,35], and others [10].…”

Section: Introductionmentioning

confidence: 99%

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Eosinophil Count as Predictive Biomarker of Immune-Related Adverse Events (irAEs) in Immune Checkpoint Inhibitors (ICIs) Therapies in Oncological Patients

Giommoni

Giorgione

Paderi

et al. 2021

Immuno

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Background: To date, no biomarkers are effective in predicting the risk of developing immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs). This study aims to evaluate the association between basal absolute eosinophil count (AEC) and irAEs during treatment with ICIs for solid tumors. Methods: We retrospectively evaluated 168 patients with metastatic melanoma (mM), renal cell carcinoma (mRCC), and non-small cell lung cancer (mNSCLC) receiving ICIs at our medical oncology unit. By combining baseline AEC with other clinical factors, we developed a mathematical model for predicting the risk of irAEs, which we validated in an external cohort of patients. Results: Median baseline AEC was 135/µL and patients were stratified into two groups accordingly; patients with high baseline AEC (>135/µL) were more likely to experience toxicity (p = 0.043) and have a better objective response rate (ORR) (p = 0.003). By constructing a covariance analysis model, it emerged that basal AEC correlated with the risk of irAEs (p < 0.01). Finally, we validated the proposed model in an independent cohort of 43 patients. Conclusions: Baseline AEC could be a predictive biomarker of ICI-related toxicity, as well as of response to treatment. The use of a mathematical model able to predict the risk of developing irAEs could be useful for clinicians for monitoring patients receiving ICIs.

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A Retrospective Analysis of Eosinophilia as a Predictive Marker of Response and Toxicity to Cancer Immunotherapy

Cited by 26 publications

References 17 publications

Immune‐related adverse events predict responses to PD‐1 blockade immunotherapy in hepatocellular carcinoma

Immune‐related adverse events predict responses to PD‐1 blockade immunotherapy in hepatocellular carcinoma

White Blood Cells in Patients Treated with Programmed Cell Death-1 Inhibitors for Non-small Cell Lung Cancer

Eosinophil Count as Predictive Biomarker of Immune-Related Adverse Events (irAEs) in Immune Checkpoint Inhibitors (ICIs) Therapies in Oncological Patients

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